The broad objective of the proposed research is to study the effects of pineal cells derived from neonatal rats on the growth and development of cells derived from sympathetic tissue in these same animals. Both types of cells, grown alone or in coculture, can be maintained for extended periods in monolayer tissue culture. The developmental course of enzymes important to pineal (serotonin N-acetyltransferase) and sympathetic tissue (tyrosine hydroxylase and choline acetyltransferase) must be characterized. Developmental alterations in phase contrast and ultrastructural morphology must be described. Preliminary results presented in this proposal will show that the pineal can have a marked effect on the developmental course of sympathetic tissue. If this effect can be better characterized, it may yield a clue as to the etiology of the devastating genetic disorder of children known as familial dysautonomia, in which low birth weights, diminished intelligence quotient, and alterations in sensory and sympathetic function are prominent clinical features. This disease may cause death in infancy or childhood. With increased knowledge of this effect, perhaps a therapy for familial dysautonomia can be devised.